Evidence from the experimental animal literature indicates that gonadal hormones such as estrogen alter immunologic function. Similar, though less conclusive human evidence has led to the idea that differences between males and females in the levels of these hormones are responsible for sex differences in immunologically-related disorders, such as some forms of autoimmune and neoplastic disease. However, the underlying hypothesis that gonadal hormones modulate immune function in humans has never been tested in an experimental paradigm which enables systematic, long term experimenter control over physiological levels of gonadal hormones in a nonclinical population. The present proposal provides such a test. Our currently funded research program, which will assess the relationship between gonadal hormones and cardiovascular response to acute stress, includes a powerful experimental paradigm uniquely suited to study the effects of ovarian hormones on physiological function. Beginning in July of 1991, naturally cycling, healthy women will be assessed for baseline values and stress-induced changes in several cardiovascular, endocrine and lipid functions before and during a complete suppression of ovarian hormones, which is produced by administration of a GnRH analogue. The contribution of estrogen to such changes will be determined by comparing women who are subsequently allowed to resume their cycle with those kept on the GnRH suppression and given estradiol replacement. The major aim of this proposal is to extend the above study to the immune system by incorporating measures of humoral and cell-mediated immunity into the protocol for the same subject population. We will ask whether suppression of ovarian hormones in healthy women alters baseline and stress-induced changes in immunologic function and whether such changes can be reversed by estrogen replacement. We will also determine the relationship among the immunologic, cardiovascular and neuroendocrine responses to reproductive hormones and to stress. This proposal is significant because it addresses an important question of women's health dealing with the relationship between ovarian hormones and immune function.